Chang Liu / Daming Zhou / Rungtiwa Nutalai / Helen M E Duyvesteyn / Aekkachai Tuekprakhon / Helen M Ginn / Wanwisa Dejnirattisai / Piyada Supasa / Alexander J Mentzer / Beibei Wang / James Brett Case / Yuguang Zhao / Donal T Skelly / Rita E Chen / Sile Ann Johnson / Thomas G Ritter / Chris Mason / Tariq Malik / Nigel Temperton / Neil G Paterson / Mark A Williams / David R Hall / Daniel K Clare / Andrew Howe / Philip J R Goulder / Elizabeth E Fry / Michael S Diamond / Juthathip Mongkolsapaya / Jingshan Ren / David I Stuart / Gavin R Screaton /
PubMed Abstract
Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape ...Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1, and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta-infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor-binding domain (RBD). Two of these RBD-binding mAbs recognize a neutralizing epitope conserved between SARS-CoV-1 and -2, while 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y, including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses.
EMDB-13857, PDB-7q6e: Beta049 fab in complex with SARS-CoV2 beta-Spike glycoprotein, The Beta mAb response underscores the antigenic distance to other SARS-CoV-2 variants Method: EM (single particle) / Resolution: 2.7 Å
EMDB-13875, PDB-7q9p: Beta-06 fab in complex with SARS-CoV-2 beta-Spike glycoprotein Method: EM (single particle) / Resolution: 4.5 Å
PDB-7pry: Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with COVOX-45 and beta-6 Fabs Method: X-RAY DIFFRACTION / Resolution: 3.1 Å
PDB-7prz: Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with beta-22 Fabs Method: X-RAY DIFFRACTION / Resolution: 3.2 Å
PDB-7ps0: Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with beta-24 Fabs Method: X-RAY DIFFRACTION / Resolution: 2.92 Å
PDB-7ps1: Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-27 Fab Method: X-RAY DIFFRACTION / Resolution: 2.4 Å
PDB-7ps2: Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-29 and Beta-53 Fabs Method: X-RAY DIFFRACTION / Resolution: 2.99 Å
PDB-7ps3: Crystal structure of antibody Beta-32 Fab Method: X-RAY DIFFRACTION / Resolution: 1.7 Å
PDB-7ps4: Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-38 Method: X-RAY DIFFRACTION / Resolution: 1.94 Å
PDB-7ps5: Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-47 Fab Method: X-RAY DIFFRACTION / Resolution: 3.14 Å
PDB-7ps6: Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-44 and Beta-54 Fabs Method: X-RAY DIFFRACTION / Resolution: 2.26 Å
PDB-7ps7: Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-40 Fab Method: X-RAY DIFFRACTION / Resolution: 3.9 Å
PDB-7q0g: Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-49 and FI-3A Fabs Method: X-RAY DIFFRACTION / Resolution: 1.82 Å
PDB-7q0h: Crystal structure of the receptor binding domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-50 and Beta-54 Method: X-RAY DIFFRACTION / Resolution: 3.65 Å
PDB-7q0i: Crystal structure of the N-terminal domain of SARS-CoV-2 beta variant spike glycoprotein in complex with Beta-43 Method: X-RAY DIFFRACTION / Resolution: 2.39 Å
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VIRAL PROTEIN / 
